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Research article Open Access

Possible mechanisms of hypotension produced 70% alcoholic
extract of Terminalia arjuna (L.) in anaesthetized dogs
Srinivas Nammi*1, Rambabu Gudavalli1, Behara S Ravindra Babu2,
Durga S Lodagala1 and Krishna M Boini1

Address: 1Pharmacology Division, Department of Pharmaceutical Sciences, Andhra University, Visakhapatnam-530 003, Andhra Pradesh, INDIA
and 2A15, Faculty of Pharmacy, University of Sydney Sydney, NSW-2006, AUSTRALIA
Email: Srinivas Nammi* - nammi@rediffmail.com; Rambabu Gudavalli - rb_gudavalli@yahoo.com; Behara S
Ravindra Babu - bsrbabu@hotmail.com; Durga S Lodagala - ldsrinivas@rediffmail.com; Krishna M Boini - krishnamurthyboini@yahoo.com
* Corresponding author

Published: 16 October 2003 Received: 15 March 2003

Accepted: 16 October 2003
BMC Complementary and Alternative Medicine 2003, 3:5
This article is available from: http://www.biomedcentral.com/1472-6882/3/5
© 2003 Nammi et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all
media for any purpose, provided this notice is preserved along with the article's original URL.

Abstract
Background: The bark of Terminalia arjuna L. (Combretaceae) is used in Ayurveda since ancient
times for the treatment of cardiac disorders. Previous laboratory investigations have demonstrated
the use of the bark in cardiovascular complications. The present study was aimed to find the effect
of 70% alcoholic extract of Terminalia arjuna on anaesthetized dog blood pressure and probable
site of action.
Methods: Six dogs were anaesthetized with intraperitoneal injection of thiopental sodium and the
blood pressure of each dog (n = 6) was measured from the left common carotid artery connected
to a mercury manometer on kymograph. The femoral vein was cannulated for administration of
drug solutions. The extract of T. arjuna (dissolved in propylene glycol) in the dose range of 5 to 15
mg/kg were administered intravenously in a pilot study and the dose (6 mg/kg) which produced
appreciable hypotension was selected for further studies.
Results: Intravenous administration of T. arjuna produced dose-dependent hypotension in
anaesthetized dogs. The hypotension produced by 6 mg/kg dose of the extract was blocked by
propranolol but not by atropine or mepyramine maleate. This indicates that muscarinic or
histaminergic mechanisms are not likely to be involved in the hypotension produced by the extract.
The blockade by propranolol of the hypotension produced by T. arjuna indicates that the extract
might contain active compound(s) possessing adrenergic β2-receptor agonist action and/or that act
directly on the heart muscle.
Conclusion: The results indicated the likely involvement of peripheral mechanism for hypotension
produced by the 70% alcoholic extract of Terminalia arjuna and lends support for the claims of its
traditional usage in cardiovascular disorders.

Background various aspects of T. arjuna have been published [4,5].

The bark of Terminalia arjuna L. (Combretaceae) has been Both experimental and clinical studies showed the benefi-
widely used in Ayurvedic system of medicine for cardiac cial effects of the bark in congestive heart failure [6–8] and
disorders since ancient times [1–3]. Extensive reviews on in ischemic heart disease [9–14] and other cardiovascular

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BMC Complementary and Alternative Medicine 2003, 3
complications [15–19]. The aqueous extract of T. arjuna
showed contraction followed by relaxation on isolated rat
thoracic aorta [15,20]. Results from our laboratory dem-
onstrated that 70% alcoholic extract of T. arjuna reduced
the platelet count on chronic treatment to dogs [21].
Singh et al. reported that aqueous solution of 70% alco-
holic bark extract of T. arjuna produced dose-dependent
decrease in heart rate and blood pressure in dogs, though
the mechanism was not determined [22]. In the present
investigation, a systematic study was performed to find
the probable mechanism of hypotension produced by
70% alcoholic extract of T. arjuna in thiopental anaesthe-
tized dogs.
Methods
Plant material and extraction
The authenticated dried bark of Terminalia arjuna was pur-
chased from the local herbal traders and was crushed to
coarse powder 20–40 mesh size and then refluxed with
70% v/v alcohol for two hours using Soxhlett's apparatus.
The extract was filtered and the filtrate was evaporated to
dryness by rotary film evaporator. 1 g of bark extract rep-
resents 9.6 g of dried bark
Chemicals used
Acetylcholine, histamine, isoprenaline and adrenaline
were purchased from Sigma-Aldrich, St. Louis, USA. Other
drugs used were mepyramine maleate (H. Jules & Co.,
Nagpur, India), propranolol (Imperial Chemical Indus-
tries, India), heparin sodium (Biological Evans Ltd.,
Hyderabad, India), trisodium citrate (SD Fine Chemicals,
Boisar, India), thiopental and atropine sulphate (The
Central Drug House, Mumbai, India).
Animal experiments
Eight dogs of either sex weighing between 10 – 15 kg sup-
plied by Visakhapatnam Municipal Corporation were
used in the study. The animal experiments conducted in
Table 1: Influence of atropine, mepyramine and propranolol on the hypotensive response of T. arjuna in dogs.
Drug Dose (n = 6)
Before Antagonist
T. arjuna 5 mg/kg Hypotension
T. arjuna 6 mg/kg Hypotension
T. arjuna 8 mg/kg Hypotension
T. arjuna 10 mg/kg Hypotension
T. arjuna 15 mg/kg Hypotension
T. arjuna 20 mg/kg(n = 2) Severe Hypotension
NS – not studied; n – number of animals.
http://www.biomedcentral.com/1472-6882/3/5
the research work were approved by the Institutional Ani-
mal Ethics Committee and by the government regulatory
body for animal research (Regd. No. 516/01/A/CPCSEA).
Thiopental sodium was administered intraperitoneally at
a dose of 40 mg/kg body weight to anaesthetize the dogs.
The femoral vein was cannulated for administration of
subsequent doses of anaesthetic (if required) and drug
solutions.
Recording of blood pressure
Haemodynamic setup was used to record the blood pres-
sure of anaesthetized dog. The blood pressure of each ani-
mal was recorded from left common carotid artery
connected to a mercury manometer on kymograph paper.
The normal blood pressure of dogs was recorded after sta-
bilization for 30 minutes. The different doses 5, 6, 8, 10
and 15 mg/kg body weight of 70% alcoholic extract of T.
arjuna were administered to all the animals (n = 6) while
the dose 20 mg/kg body weight was studied in only 2 ani-
mals. The 6 mg/kg body weight dose of the extract which
produced appreciable blood pressure lowering activity
was used further to determine the change in its blood
pressure response before and after administration of atro-
pine (1 mg), mepyramine maleate (20 µg) and pro-
pranolol (30 µg).
Results
The extract produced dose-dependent hypotension in the
dose range of 5 to 15 mg/kg body weight while 20 mg/kg
body weight doses was found to be fatal (Table 1). The
hypotension produced by 6 mg/kg body weight was not
blocked by prior administration of atropine (1 mg) or
mepyramine maleate (20 µg) which blocked ace-
tylchloine (8 µg) and histamine (8 µg) responses respec-
tively. The hypotension of T. arjuna was blocked by
propranolol (30 µg) which blocked the isoprenaline (10
µg) response. The responses observed with 6 mg/kg dose
Response
After Antagonist
Atropine (1 mg) Mepyramine (20 Propranolol (30 µg)
µg)
NS NS NS
No Blockade No Blockade Blockade
NS NS NS
NS NS NS
NS NS NS
NS NS NS
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Effect
Figureof170% alcoholic extract of Terminalia arjuna on anaesthetized dog blood pressure
Effect of 70% alcoholic extract of Terminalia arjuna on anaesthetized dog blood pressure. TAE – 70% alcoholic
extract of Terminalia arjuna, Ach – Acetylcholine, H – Histamine, IP – Isoprenaline, M – Mepyramine, PG – Propylene glycol,
Prop – Propranolol.

of the extract before and after administration of the antag-
onists are shown in Fig 1. The vehicle propylene glycol
alone did not alter the blood pressure in the doses stud-
ied.
Discussion
The hypotension produced by 6 mg/kg body weight dose
of the extract was not blocked by atropine which could
block the response of selected dose of acetylcholine indi-
cating that the muscarinic mechanism was not involved.
Studies with mepyramine maleate indicate that
histaminergic mechanism was also not involved in the
hypotension produced by the extract. Studies with pro-
pranolol which blocked the hypotensive response of the
extract indicated that it may contain compounds having
adrenergic β-receptor agonist action. Even though pro-
pranolol is a non-specific β-blocker, it is clear that the
compounds present in the extract might be adrenergic β2-
agonists, since adrenergic β2-receptor stimulation pro-
duces hypotension. Moreover, with the limitations of our
study, one cannot completely ruled out the possibility
that the observed hypotensive responsive could also be
due to the effect of T. arjuna directly on the heart there by
reducing the cardiac load. Earlier, it was reported that
aqueous soluble fraction of 70% alcoholic extract (dried)
of T. arjuna produced dose-dependent hypotension and
decrease in heart rate [22] and were attributed to princi-
ples of the extract acting centrally. Our studies with 70%
alcoholic extract dissolved in propylene glycol indicate
the likely presence of compounds acting peripherally
through adrenergic β2-receptor mechanism and/or by
direct action on the cardiac muscle. Mallikarjuna and co-
workers [20] studied the influence of aqueous extract of T.
arjuna on isolated rat thoracic aorta and found contrac-
tion followed by relaxant effect. It was felt that the vasore-
laxant effect of T. arjuna extract could contribute to the

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reported decrease in blood pressure in anaesthetized dogs
as observed by Singh et al [22]. The same experiment on
isolated vascular smooth muscle lends support for our
observation that the hypotension could be of peripheral
origin. However, Mallikarjuna and co-workers indicated
that the vasorelaxant effect of the extract was not blocked
by propranolol. The possible reason for this variable effect
could be due to the difference in the active principles
present in different types of extracts used. This indicates
that the 70% alcoholic extract might contain compounds
to a higher degree whose activity was blocked by pro-
pranolol while the activity produced by the constituents
of aqueous extract were not blocked by propranolol. Fur-
ther investigations are needed on the isolates of Terminalia
arjuna to study their cardiovascular effects in order to
explain more in detail of the observed results.
Conclusions
The present results indicate that the 70% alcoholic extract
of Terminalia arjuna produced hypotension of peripheral
origin and support the claims of its traditional usage as
cardiovascular medicine. The observed effect could be due
to adrenergic β2-receptor agonistic and/or direct action on
the heart. Detailed studies on the active constituents are
needed which might provide new insights in cardiovascu-
lar drugs.
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15. Tripathi YB: Terminalia arjuna extract modulates the contrac-
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Res 1993, 7:320-322.
16. Vaidya AB: Terminalia arjuna in cardiovascular therapy. J Assoc
Physi Ind 1994, 42:281-282.
17. Gauthaman K, Maulik M, Kumari R, Manchanda SC, Dunda AK and
Maulik SK: Effect of chronic treatment with bark of Terminalia
arjuna : a study on the isolated ischemic reperfused rat heart.
J Ethnopharmacol 2001, 75:197-201.
18. Miller AL: Botanical influences on cardiovascular diseases. Alt
Med Rev 1998, 3:422-431.
19. Shaila HP, Udupa SL and Udupa AL: Hypolipidemic activity of
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Pre-publication history
The pre-publication history for this paper can be accessed
here:
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